Fentanyl pectin nasal spray (PecFent(R)) uses a novel pectin-based delivery system that turns from an aqueous solution into a gel when applied to mucosal surfaces. Fentanyl is absorbed in a controlled manner from the pectin gel formed in the nasal cavity, and has a rapid onset of pain relief and duration of action that matches the time course of a typical episode of breakthrough pain in cancer (BTPc). Relative to administration as oral transmucosal fentanyl, fentanyl administered as fentanyl pectin nasal spray is more rapidly absorbed, reaches higher maximum plasma concentrations and has greater bioavailability. In the treatment of BTPc in two randomized, double-blind, crossover trials in opioid-tolerant adults, fentanyl pectin nasal spray (100-800 mug titrated doses) was significantly more effective than placebo in reducing pain intensity and provided a significantly faster onset of pain relief than oral immediate-release morphine. During long-term treatment of BTPc episodes, fentanyl pectin nasal spray consistently provided effective pain relief in an open-label, 16-week trial. Most patients were satisfied or very satisfied with the ease of use and convenience of the nasal spray. Fentanyl pectin nasal spray 100-800 mug was generally well tolerated and was not associated with nasal tolerability problems.